Alternative titles; symbols
ORPHA: 93334;
Cytogenetic location: 13q21-q32 Genomic coordinates (GRCh38): 13:54,700,001-101,100,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 13q21-q32 | Postaxial polydactyly, type A2 | 602085 | Autosomal dominant | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of postaxial polydactyly, see 174200.
Van der Zwaag et al. (2010) studied a 27-month-old boy who was born with bilateral postaxial polydactyly of the hands. The extra sixth digits, which were removed surgically, consisted of soft tissue only, although a nail was present on the left sixth digit. In addition, the boy had an anteriorly placed anus, with remnants of a spontaneously ruptured anal membrane that was treated with dilation only. Examination at 8 months of age showed macrocephaly and mild facial dysmorphism, including broad nasal bridge, telecanthus, and frontal bossing; his ears were slightly rotated and had small lobules, with a left-sided preauricular tag. At 27 months of age, he had normal psychomotor development and persistent but nonprogressive macrocephaly. The parents, who were a nonconsanguineous Caucasian and Africo-South American couple, were normocephalic. A half brother of the proband's mother was reported by family history to have had polydactyly of both hands and feet; he died at 4 days of age, but the cause of death was unknown.
Akarsu et al. (1997) performed a linkage study in a family with postaxial polydactyly type A (PAPA). The family showed a total of 18 informative meioses of which 11 were phase-known. Akarsu et al. (1997) excluded linkage to 7p15-q11.23, where a form of PAPA (PAPA1; 174200) had been mapped in a large Indian kindred. They demonstrated linkage to markers from 13q21-q32. A maximum lod score of 2.35 at 7 cM was found with D13S1230. They observed no recombination in affected members between centromeric D13S800 and telomeric D13S154 in a 23-cM interval. One unaffected member of the family received the 'affected haplotype' from his affected parent. Coding this individual as of 'unknown' status, they obtained the highest lod score with D13S1230 (maximum lod = 3.612 with no recombination).
In a boy with bilateral postaxial polydactyly of the hands, van der Zwaag et al. (2010) performed standard karyotyping and found heterozygosity for a de novo inverted duplication in the long arm of chromosome 13. FISH analysis confirmed that the aberrant chromosome 13 consisted solely of chromosome 13 material and that the centromere and telomere of both chromosomes 13 were intact. Array CGH showed a 5.59-Mb gain in chromosome 13 bands 13q31.3 and 13q32.1, from base 89,665,466 to 95,252,224 (NCBI36) from the 13p telomere, and no other abnormalities larger than 4 probes were noted, thus excluding well-known benign copy number variants.
Associations Pending Confirmation
For discussion of a possible association between postaxial polydactyly type A and mutation in the DACH1 gene, see 603803.0001.
Exclusion Studies
By mutation analysis, Ayres et al. (2001) eliminated the DACH1 gene as a candidate gene for postaxial polydactyly type A in a family with linkage to chromosome 13q21-q32.
Akarsu, A. N., Ozbas, F., Kostakoglu, N. Mapping of the second locus of postaxial polydactyly type A(PAP-A2) to chromosome 13q21-q32. (Abstract) Am. J. Hum. Genet. 61 (suppl.): A265 only, 1997.
Ayres, J. A., Shum, L., Akarsu, A. N., Dashner, R., Takahashi, K., Ikura, T., Slavkin, H. C., Nuckolls, G. H. DACH: genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue. Genomics 77: 18-26, 2001. [PubMed: 11543628] [Full Text: https://doi.org/10.1006/geno.2001.6618]
van der Zwaag, P. A., Dijkhuizen, T., Gerssen-Schoorl, K. B. J., Colijn, A. W., Broens, P. M. A., Flapper, B. C. T., van Ravenswaaij-Arts, C. M. A. An interstitial duplication of chromosome 13q31.3q32.1 further delineates the critical region for postaxial polydactyly type A2. Europ. J. Med. Genet. 53: 45-49, 2010. [PubMed: 19941983] [Full Text: https://doi.org/10.1016/j.ejmg.2009.11.003]